患有中风的新生儿中的抗磷脂抗体——抗磷脂综合征的一种独特实体还是变体？

Antiphospholipid antibodies in neonates with stroke--a unique entity or variant of antiphospholipid syndrome?

作者信息

Berkun Y, Simchen M J, Strauss T, Menashcu S, Padeh S, Kenet G

机构信息

Departments of Pediatrics; Obstetrics and Gynecology; Neonatology; Pediatric Neurology; National Hemophilia Center and Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Israel and Sackler Medical School, Tel Aviv University, Tel Aviv, Israel Departments of Pediatrics; Obstetrics and Gynecology; Neonatology; Pediatric Neurology; National Hemophilia Center and Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer, Israel and Sackler Medical School, Tel Aviv University, Tel Aviv, Israel.

出版信息

Lupus. 2014 Sep;23(10):986-93. doi: 10.1177/0961203314531842. Epub 2014 Apr 11.

DOI:10.1177/0961203314531842

PMID:24729280

Abstract

OBJECTIVE

YB current affiliation: Department of Pediatrics, Hadassah-Hebrew University Medical Center, Mount Scopus, Israel YB and MJS contributed equally to the study and should be regarded as joint first authors on this manuscript. Antiphospholipid syndrome (APS) may present with thrombosis and persistently elevated titers of antiphospholipid antibodies (aPL) in the neonatal period. Our aim was to investigate the course and impact of elevated titers of aPL in a cohort of infants presenting with either perinatal arterial ischemic stroke (PAS) or cerebral sinus vein thrombosis (CSVT) during the perinatal period.

STUDY DESIGN

Sixty-two infants with clinically and radiologically confirmed PAS or CSVT presenting in the neonatal period underwent thrombophilia workup that included Factor V Leiden (FVL), PII20210A mutation, MTHFR 677T polymorphism, protein C, protein S, aPL namely either circulating lupus anticoagulant (CLA), anticardiolipin antibodies (aCL) or anti-β2-glycoprotein-1 (β2GP1). Mothers also underwent thrombophilia workup.

RESULTS

Twelve infants with persistently elevated aPL were prospectively followed. Infants with positive aPL showed no concordance with presence of maternal aPL. All children were followed for a median of 3.5 years (range: nine months to 19 years) with repeated aPL testing every three to six months. Anticoagulant therapy initiation and therapy duration varied at the physician's discretion. In 10/12 cases aPL decreased to normal range within 2.5 years; one female with complex thrombophilia risk factors required indefinite prolonged anticoagulation. None of the infants showed recurrent thrombosis or any other APS manifestations, despite lack of prolonged anticoagulation.

CONCLUSIONS

The presence of aPL may be important in the pathogenesis of cerebral thrombosis in neonates. Nevertheless, the nature of thrombophilia interactions in this period and their therapeutic impact warrants further investigation.

摘要

目的

YB目前任职于以色列斯科普斯山哈达萨-希伯来大学医学中心儿科。YB和MJS对本研究贡献相同，应被视为本文的共同第一作者。抗磷脂综合征（APS）在新生儿期可能表现为血栓形成以及抗磷脂抗体（aPL）滴度持续升高。我们的目的是调查在围产期出现围产期动脉缺血性卒中（PAS）或脑静脉窦血栓形成（CSVT）的一组婴儿中，aPL滴度升高的病程及影响。

研究设计

62例在新生儿期出现临床和影像学确诊的PAS或CSVT的婴儿接受了血栓形成倾向检查，包括凝血因子V莱顿（FVL）、凝血酶原G20210A突变、亚甲基四氢叶酸还原酶（MTHFR）677T多态性、蛋白C、蛋白S、aPL，即循环狼疮抗凝物（CLA）、抗心磷脂抗体（aCL）或抗β2糖蛋白1（β2GP1）。母亲们也接受了血栓形成倾向检查。

结果

对12例aPL持续升高的婴儿进行了前瞻性随访。aPL阳性的婴儿与母亲aPL的存在情况不一致。所有儿童的随访时间中位数为3.5年（范围：9个月至19岁），每三到六个月重复进行aPL检测。抗凝治疗的开始和疗程由医生酌情决定。在12例中的10例中，aPL在2.5年内降至正常范围；一名具有复杂血栓形成倾向危险因素的女性需要无限期延长抗凝治疗。尽管没有进行长期抗凝治疗，但没有婴儿出现复发性血栓形成或任何其他APS表现。